Plasma Exosomes as a Therapeutic Approach Prevent the Cognitive Decline by Inhibiting Tau Protein Hyperphosphorylation in Alzheimer’s Disease Mice

2021 ◽  
Vol 11 (2) ◽  
pp. 221-228
Author(s):  
Lijuan Huang ◽  
Hao Wang ◽  
Haijuan Sui ◽  
Yijie Shi ◽  
Liang Zhao
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Therapeutic Approach ◽  
Bioinformatics Analysis ◽  
Cognitive Impairments ◽  
Cognitive Disorder ◽  
Pathological Process ◽  
Exosomal Mirnas ◽  
Novel Therapeutic

It was well known that circulating plasma exosomes (Pla-Exo) were enriched with multiple microRNAs (miRNAs) and participated in the regulation of biological and pathological process via exchanging information and transferring substance into targeted cells and organs. Therefore, clinical significance of Pla-Exo had been recognized and they functioned as biomarkers for the clinical diagnosis or therapeutic applications to treat diseases. We explored the possibility of using Pla-Exo as a novel therapeutic approach for ameliorating cognitive dysfunction in Alzheimer’s disease (AD) mice. Here we found that Pla-Exo freely crossed the blood-brain barrier (BBB) and was transferred into the hippocampus of mice. After following peritoneal injection (I.P.) of Pla-Exo, survival of neuron cells was enhanced and cognitive disorder was attenuated in okadaic acid (OA) treated mice via deactivating GSK-3β and down-regulating GSK-3β mediated hyperphosphorylation of Tau protein. Finally, some potential exosomal miRNAs were screened by bioinformatics analysis and confirmed their target of GSK-3β. Taken together, all data proved that Pla-Exo contributed to the amelioration of cognitive impairments.

P2-064: The tau protein: From physiological to pathological process in Alzheimer's disease

2013 ◽  
Vol 9 ◽  
pp. P366-P366
Author(s):  
Paola Flores ◽  
Raúl Mena López ◽  
Benjamín Floran ◽  
José Segovia-Vila ◽  
José Luna-Muñoz
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Pathological Process

P2-368: Innate immunity stimulation as a novel therapeutic approach in Alzheimer's disease

2012 ◽  
Vol 8 (4S_Part_11) ◽  
pp. P392-P392 ◽  
Author(s):  
Henrieta Scholtzova ◽  
Fernando Goni ◽  
Jason Pan ◽  
Yanjie Sun ◽  
Jialin Li ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Innate Immunity ◽  
Therapeutic Approach ◽  
Novel Therapeutic

P4-018: Innate Immunity Stimulation Via Toll-Like Receptor 9 as a Novel Therapeutic Approach in Alzheimer’s Disease

2016 ◽  
Vol 12 ◽  
pp. P1021-P1022 ◽  
Author(s):  
Henrieta Scholtzova ◽  
Pramod N. Nehete ◽  
Bharti P. Nehete ◽  
Elizabeth Cho ◽  
Melanie M. Mallory ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Innate Immunity ◽  
Therapeutic Approach ◽  
Toll Like Receptor ◽  
Novel Therapeutic

scholarly journals Antioxidant, Anti-inflammatory and Neuroprotective Profiles of Novel 1,4-Dihydropyridine Derivatives for the Treatment of Alzheimer’s Disease

Antioxidants ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 650
Author(s):  
Patrycja Michalska ◽  
Paloma Mayo ◽  
Cristina Fernández-Mendívil ◽  
Giammarco Tenti ◽  
Pablo Duarte ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Tau Protein ◽  
Hippocampal Slices ◽  
Antioxidant Properties ◽  
Neuronal Loss ◽  
Pathological Process ◽  
Anti Inflammatory ◽  
Gsk 3Β

Alzheimer’s disease is a chronic and irreversible pathological process that has become the most prevalent neurodegenerative disease. Currently, it is considered a multifactorial disease where oxidative stress and chronic neuroinflammation play a crucial role in its onset and development. Its characteristic neuronal loss has been related to the formation of neurofibrillary tangles mainly composed by hyperphosphorylated tau protein. Hyperphosphorylation of tau protein is related to the over-activity of GSK-3β, a kinase that participates in several pathological mechanisms including neuroinflammation. Neuronal loss is also related to cytosolic Ca2+ homeostasis dysregulation that triggers apoptosis and free radicals production, contributing to oxidative damage and, finally, neuronal death. Under these premises, we have obtained a new family of 4,7-dihydro-2H-pyrazolo[3–b]pyridines as multitarget directed ligands showing potent antioxidant properties and able to scavenge both oxygen and nitrogen radical species, and also, with anti-inflammatory properties. Further characterization has demonstrated their capacity to inhibit GSK-3β and to block L-type voltage dependent calcium channels. Novel derivatives have also demonstrated an interesting neuroprotective profile on in vitro models of neurodegeneration. Finally, compound 4g revokes cellular death induced by tau hyperphosphorylation in hippocampal slices by blocking reactive oxygen species (ROS) production. In conclusion, the multitarget profile exhibited by these compounds is a novel therapeutic strategy of potential interest in the search of novel treatments for Alzheimer’s disease.

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